AzTrials
AzTrials

Autoimmune DiseasesPhase 2NCT03183869

Fecal Microbial Transplantation in Relapsing Multiple Sclerosis Patients

A Phase 2 study testing Fecal microbiota in people with Autoimmune Diseases and Relapsing Multiple Sclerosis, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

The proposed randomized, open label, with treat as usual control group (standard treatment or any disease modifying drugs), crossover phase II study will be conducted in 40 patients (n=20 per group) with the relapsing forms of multiple sclerosis according to the McDonald 2010 Criteria. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
What is being tested?
Fecal microbiota
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
1 siteCanada
Study dates
24 Aug 2017to 25 Jan 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Have a confirmed diagnosis of relapsing MS defined by the 2010 Revised McDonald Criteria for the Diagnosis of Multiple Sclerosis
  • Any disease duration will be accepted.
  • Have a baseline EDSS of = or <7.0
  • Older than 18 years of age.
  • Be able to attend all clinic appointments without interruption
  • Patients must be able to understand English sufficiently well to understand and comply with the clinic and medication schedules and procedures.
  • Be willing and able to give written informed consent
  • Negative blood pregnancy test at screening

Who cannot join

  • Not meeting all of the above inclusion criteria
  • Pregnancy or breastfeeding
  • Current or recent [in the last 90 days] exposure to high dose corticosteroids
  • Ongoing use of antibiotics
  • Standard of care exclusions for MRI scans
  • Presence of a chronic intestinal disease e.g. Celiac, malabsorption, colonic tumor
Show all 11Show fewer
  • Inability to provide informed written consent.
  • Immunosuppression from transplantation, HIV, cancer chemotherapy or ongoing use of any immunosuppressive agents.
  • Concomitant inflammatory diseases
  • Pregnant women
  • Any contra-indications for MRI. Participants are to be screened by a CMRTO (The College of Medical Radiation Technologists of Ontario) certified MRI Technologist in order to determine the MRI compatibility or exclusion of implantable/external devices according to the manufacturer's safety guidelines. The devises include cerebral aneurysm clips, neuro-stimulator, mechanical heart valves, cardiac stents, IUDs(intrauterine device), vena cava filters, shunts, embolization coils, cochlear implants, non-removable prosthesis/artificial limbs. Contraindications are pacemaker of defibrillator, shrapnel/metallic fragments, previous brain surgery, seizure, severe claustrophobia, weight or body index that will prevent a successful MRI study

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • London Health Sciences Centre, University Hospital

    London, Ontario, N6A 5A5

Other trials in Canada

About this study

The proposed randomized, open label, with treat as usual control group (standard treatment or any disease modifying drugs), crossover phase II study will be conducted in 40 patients (n=20 per group) with the relapsing forms of multiple sclerosis according to the McDonald 2010 Criteria.

Patients will be randomized into 2 intervention groups. One will receive the FMT from month 1 and for the first 6 months (early intervention group). On the other hand, the other group will be a control group during the first 6 months and will receive the FMT for the last 6 months of the study. Patients will be screened for eligibility based on MS diagnosis and EDSS and if eligible then consented. All qualified patients will not be currently or recently treated with high dose steroids.

Read the detailed description

At Visit 1, before FMT(fecal microbial transplantation), patients will be evaluated for their vital signs, medical history and concomitant medications. Also before transplantation, patient's stool will be collected to study their microbial profile, blood collected for analysis to evaluate cytokines levels as well as blood DNA bacteria and finally, urinalysis to assess gut permeability (baseline). Other assessments (prior to the first dose of therapy) include an Expanded Disability Status Scale (EDSS), pregnancy test (if applicable), physical exam and ECG. Blood samples are also taken at month 1 in order to establish a baseline for routine chemistry/hematology. After all these assessments FMT will be performed by a trained nurse via a rectal enema.

FMT for the early intervention group will be at V1, 2, 2.1, 2.2, V3 and V4. FMT randomized to late intervention group will be V4, 5, 6, 6.1.6.2, 6.3 and V7

Both groups, at Visit 1, Visit 4 and Visit 7, patients will be instructed to drink lactulose solution and collect the urine throughout the previous night and first thing in the morning. A proper collecting bottle will be provided and will also undergo a contrast-enhanced brain MRI scan at Robarts Institute London Ontario.

Those randomized to the Early Intervention group, will return to the clinic for visit 2, 1 month after the first FMT(fecal microbial transplantation). Another stool sample to evaluate the microbial before the second FMT will be collected and peripheral blood samples for cytokines and blood bacterial DNA analysis. Both groups this same routine procedure repeated at visits 2.1, 2.2, 3, 4, 5, 6, 6.1.6.2, 6.3 and visit 7. Another safety assessment 2 weeks after FMT is to review any adverse events that may have occurred.

Both groups will have an MRI at M1, M6 and M12.

Being tested
Fecal microbiota
Keywords
microbiome, multiple sclerosis, microbiota, gut
Medical subject headings
Autoimmune Diseases, Multiple Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Fecal microbiotaDrug

    Also called fecal microbial transplantation

    fecal microbial transplantation

Study groups in NCT03183869
Study groupRoleWhat they receive
Early InterventionActive comparatorFecal microbiota via enema at Month 1, 2, 3. 4, 5 and month 6 along with stool, urine and blood collection. At months 7, 8, 9, 10, 11 and 12 only stool, urine and blood collection.
Receives: Drug: Fecal microbiota
Late InterventionActive comparatorAt months 1, 2, 3, 4, 5 and 6, stool, urine and blood collection. Fecal microbiota via enema at month 6, 7, 8, 9, 10, 11and 12 months along with stool, urine and blood collection.
Receives: Drug: Fecal microbiota

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Effect of Fecal Microbial Transplantation in Peripheral Blood Cytokines Within Relapsing Multiple Sclerosis Patients

    Luminex test to evaluate the levels of 25 cytokines in peripheral blood pre-fecal transplant and post fecal transplant. Due to early termination of the trial, we didn't meet the number of participants required for statistical analysis; therefore, we analyzed the data pre and post FMT, rather than early and late intervention groups as originally planned. Due to the small sample size there was a large variation between cytokine levels of each participant for pre and post FMT, resulting in large standard deviations.

    Measured: Within 6 months

Secondary outcomes (4)

  1. Evaluate Effect of Fecal Microbial Transplantation in Gut Microbiome

    PCR (polymerase chain reaction) to assess blood DNA bacteria

    Measured: Monthly for 6 months

  2. Evaluate Effect of Fecal Microbial Transplantation in Gut Permeability

    Urinalysis to evaluate lactulose and mannitol levels

    Measured: Baseline, 6 months, 12 months

  3. Evaluate Treatment Clinical Safety: Neurological Exam Using the Expanded Disability Status Scale

    Neurological exam using the Expanded Disability Status Scale

    Measured: Monthly for 6 months

  4. Evaluate Treatment Safety: MRI to Access Subclinical Disease Activity

    MRI to access subclinical disease activity

    Measured: Baseline, 6 months and 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jun 2017
  2. Study start24 Aug 2017
  3. Primary completion19 Nov 2018
  4. Study completion25 Jan 2019

Why it stopped: Primary Investigator passed away.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Model description
This is a prospective, cross-over, open label, randomized 1:1 early versus delayed groups, interventional \[FMT\] versus no interventional \[no FMT\] controlled trial to explore the effects of FMT from a healthy donor to RMS patients and investigate whether this can influence disease activity based on a panel of biological markers.
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03183869
Sponsor's protocol ID
MS-FMT-001
Status last verified
Nov 2019
First submitted
9 May 2017
Last updated
2 Dec 2019
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Cantarel BL, Waubant E, Chehoud C, Kuczynski J, DeSantis TZ, Warrington J, Venkatesan A, Fraser CM, Mowry EM. Gut microbiota in multiple sclerosis: possible influence of immunomodulators. J Investig Med. 2015 Jun;63(5):729-34. doi: 10.1097/JIM.0000000000000192.

    PubMed 25775034

  • Miyake S, Kim S, Suda W, Oshima K, Nakamura M, Matsuoka T, Chihara N, Tomita A, Sato W, Kim SW, Morita H, Hattori M, Yamamura T. Dysbiosis in the Gut Microbiota of Patients with Multiple Sclerosis, with a Striking Depletion of Species Belonging to Clostridia XIVa and IV Clusters. PLoS One. 2015 Sep 14;10(9):e0137429. doi: 10.1371/journal.pone.0137429. eCollection 2015.

    PubMed 26367776

  • Tremlett H, Fadrosh DW, Faruqi AA, Hart J, Roalstad S, Graves J, Lynch S, Waubant E; US Network of Pediatric MS Centers. Gut microbiota composition and relapse risk in pediatric MS: A pilot study. J Neurol Sci. 2016 Apr 15;363:153-7. doi: 10.1016/j.jns.2016.02.042. Epub 2016 Feb 20.

    PubMed 27000242

  • Lavasani S, Dzhambazov B, Nouri M, Fak F, Buske S, Molin G, Thorlacius H, Alenfall J, Jeppsson B, Westrom B. A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL-10 producing regulatory T cells. PLoS One. 2010 Feb 2;5(2):e9009. doi: 10.1371/journal.pone.0009009.

    PubMed 20126401

  • Kelly CR, de Leon L, Jasutkar N. Fecal microbiota transplantation for relapsing Clostridium difficile infection in 26 patients: methodology and results. J Clin Gastroenterol. 2012 Feb;46(2):145-9. doi: 10.1097/MCG.0b013e318234570b.

    PubMed 22157239

  • Kwon HK, Kim GC, Kim Y, Hwang W, Jash A, Sahoo A, Kim JE, Nam JH, Im SH. Amelioration of experimental autoimmune encephalomyelitis by probiotic mixture is mediated by a shift in T helper cell immune response. Clin Immunol. 2013 Mar;146(3):217-27. doi: 10.1016/j.clim.2013.01.001. Epub 2013 Jan 16.

    PubMed 23416238

  • Mielcarz DW, Kasper LH. The gut microbiome in multiple sclerosis. Curr Treat Options Neurol. 2015 Apr;17(4):344. doi: 10.1007/s11940-015-0344-7.

    PubMed 25843302

  • Hooper LV, Littman DR, Macpherson AJ. Interactions between the microbiota and the immune system. Science. 2012 Jun 8;336(6086):1268-73. doi: 10.1126/science.1223490. Epub 2012 Jun 6.

    PubMed 22674334

  • Wang S, Xu M, Wang W, Cao X, Piao M, Khan S, Yan F, Cao H, Wang B. Systematic Review: Adverse Events of Fecal Microbiota Transplantation. PLoS One. 2016 Aug 16;11(8):e0161174. doi: 10.1371/journal.pone.0161174. eCollection 2016.

    PubMed 27529553

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Fecal microbiota in people with Autoimmune Diseases and Relapsing Multiple Sclerosis, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 2 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Effect of Fecal Microbial Transplantation in Peripheral Blood Cytokines Within Relapsing Multiple Sclerosis Patients (time frame: Within 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03183869, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2019.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in